PROJECT SUMMARY/ ABSTRACT This is a NIH Pathway to Independence Award (K99/R00) application intended to promote the career of Dr. Priya Palta, PhD, a postdoctoral fellow at the University of North Carolina at Chapel Hill, to a path of independent research. Dr. Palta is a trained epidemiologist with a multidisciplinary record of research in the epidemiology of cardiovascular disease (CVD), aging, and CVD risk factors for cognitive decline and dementia. Her goal is to build on these skills through focused training in neuroscience to become an independent scientist at the interface of neuroscience and population sciences, for innovative work on modifiable targets that influence pathways associated with age-related cognitive decline. The topical areas of the proposed training and subsequent research are physical activity, age-related cognitive decline, neuroimaging, and neurotrophic factors reported to link physical activity with increased neuroplasticity. K99 Career development aim: Obtain transdisciplinary competencies in the biochemical and neural pathways that underlie cognitive function, including neurotrophic biomarkers and neuroimaging modalities through a didactic and experiential curriculum complemented by a novel prospective population-based study. These activities will be supervised by lead mentor Dr. Gerardo Heiss, MD PhD, Kenan Distinguished Professor of Epidemiology and co-mentors Dr. Kelly Evenson, PhD, Research Professor of Epidemiology, and Dr. Thomas Mosley, PhD, Professor of Medicine (Geriatrics) and Neurology. A team of collaborators with complementary expertise will supplement Dr. Palta's training in specific areas. The team of mentors and collaborators is fully committed to assisting Dr. Palta reach her research training and career development goals and to ensure her successful transition to independent researcher. Post-mentored R00 phase: Dr. Palta will apply the K99 competencies to develop an innovative R00 project nested in the cohort of the ongoing Atherosclerosis Risk in Communities (ARIC) Study. For this, physical activity over 23 years and neurotrophic markers (BDNF and IGF-1) measured on the ARIC participants will be related to repeat cognitive assessments, gray matter hippocampal volumes, and adjudicated mild cognitive impairment (MCI) and Alzheimer's disease (AD). Anticipated results: Through this Pathway to Independence Award, Dr. Palta will acquire (1) in-depth multidisciplinary training in the measurement, analysis and interpretation of (a) neurotrophic biomarkers and (b) neuroimaging outcomes for their application in population-based studies and (2) apply these new competencies to an innovative research question on the biochemical and neural links between physical activity and neurocognitive outcomes. This proposal will contribute novel science in the (1) critical assessment of the role of midlife physical activity in delaying cognitive impairment, (2) on the population distribution of BDNF and IGF-1 and its associations with physical activity and neurocognitive outcomes, and (3) targets for community-based lifestyle and physical activity programs to impact cognitive aging.